1257517-84-2Relevant academic research and scientific papers
Chiral Dihydrobenzofuran Acids Show Potent Retinoid X Receptor-Nuclear Receptor Related 1 Protein Dimer Activation
Sundén, Henrik,Sch?fer, Anja,Scheepstra, Marcel,Leysen, Seppe,Malo, Marcus,Ma, Jian-Nong,Burstein, Ethan S.,Ottmann, Christian,Brunsveld, Luc,Olsson, Roger
, p. 1232 - 1238 (2016)
The nuclear receptor Nurr1 can be activated by RXR via heterodimerization (RXR-Nurr1) and is a promising target for treating neurodegenerative diseases. We herein report the enantioselective synthesis and SAR of sterically constricted benzofurans at RXR. The established SAR, using whole cell functional assays, lead to the full agonist 9a at RXR (pEC50 of 8.2) and RXR-Nurr1. The X-ray structure shows enantiomeric discrimination where 9a optimally addresses the ligand binding pocket of RXR.
Asymmetric synthesis of a tricyclic benzofuran motif: A privileged core structure in biologically active molecules
Sunden, Henrik,Olsson, Roger
, p. 4831 - 4833 (2010)
An efficient synthetic strategy for the asymmetric synthesis of a hexahydrodibenzofuran core structure, with a quaternary stereogenic center, emerges by employing a chiral reduction using Corey's (S)-Me-CBS-oxazaborolidine reagent followed by a Mitsunobu reaction to set the stereochemistry. A Pd-mediated intramolecular Heck reaction concludes the tricyclic core structure. Finally, a Pd/C catalyzed reduction yields the target molecule in 21% overall yield over 6 steps.
Design of a highly selective and potent class of non-planar estrogen receptorβ agonists
Sunden, Henrik,Ma, Jian-Nong,Hansen, Lars K.,Gustavsson, Anna-Lena,Burstein, Ethan S.,Olsson, Roger
, p. 1283 - 1294 (2013/08/23)
Selective activation of the estrogen receptorβ (ERβ) could be a safe approach to hormone replacement therapy for both women and men, in contrast to the estrogens currently used for women which activate both ERβ and ERα, occasionally causing severe side effects. The selective ERβ agonist AC-131 has shown efficacy in animal models of Parkinson's disease and neuropathic pain. With the use of AC-131 as template, herein we report the discovery, synthesis, and structure-activity relationship (SAR) study of a new class of dihydrobenzofurans as potent and selective ERβ agonists. The SAR was established by enantioselective synthesis, molecular modeling, and whole-cell-based functional assays. The most potent diastereomer, cis-10-SR, was shown to have an EC50 value of A T-shaped trans-SS diastereomer of 4-{3-fluoro-8-oxatricyclo[7.5.0.02,7]tetradeca-2,4,6-trien-1-yl}phenol (10) was found to be 1000-fold selective for ERβ over ERα.
